Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.
School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.
Genes Dev. 2018 Dec 1;32(23-24):1562-1575. doi: 10.1101/gad.317362.118. Epub 2018 Nov 26.
Heat shock factor 1 (HSF-1) and forkhead box O (FOXO) are key transcription factors that protect cells from various stresses. In , HSF-1 and FOXO together promote a long life span when insulin/IGF-1 signaling (IIS) is reduced. However, it remains poorly understood how HSF-1 and FOXO cooperate to confer IIS-mediated longevity. Here, we show that prefoldin 6 (PFD-6), a component of the molecular chaperone prefoldin-like complex, relays longevity response from HSF-1 to FOXO under reduced IIS. We found that PFD-6 was specifically required for reduced IIS-mediated longevity by acting in the intestine and hypodermis. We showed that HSF-1 increased the levels of PFD-6 proteins, which in turn directly bound FOXO and enhanced its transcriptional activity. Our work suggests that the prefoldin-like chaperone complex mediates longevity response from HSF-1 to FOXO to increase the life span in animals with reduced IIS.
热休克转录因子 1（HSF-1）和叉头框 O（FOXO）是保护细胞免受各种应激的关键转录因子。在这篇论文中，当胰岛素/胰岛素样生长因子 1 信号（IIS）降低时，HSF-1 和 FOXO 共同促进了较长的寿命。然而，HSF-1 和 FOXO 如何合作赋予 IIS 介导的长寿仍然知之甚少。在这里，我们表明，伴侣蛋白 Prefoldin 6（PFD-6），分子伴侣 Prefoldin-like 复合物的一个组成部分，在 IIS 降低的情况下，将长寿反应从 HSF-1 传递给 FOXO。我们发现 PFD-6 通过在肠和皮下组织中发挥作用，是 IIS 介导的长寿所必需的。我们表明，HSF-1 增加了 PFD-6 蛋白的水平，这些蛋白反过来直接与 FOXO 结合并增强了其转录活性。我们的工作表明，Prefoldin-like 伴侣蛋白复合物介导了从 HSF-1 到 FOXO 的长寿反应，从而增加了 IIS 降低的动物的寿命。
